Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL

August 3, 2022 updated by: Kartos Therapeutics, Inc.

An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma or Relapsed/Refractory Chronic Lymphocytic Leukemia

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, combined with acalabrutinib for the treatment of adults with Diffuse Large B-Cell Lymphoma and Chronic Lymphocytic Leukemia. Participants must be relapsed/refractory (having failed prior therapy)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

84

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
      • Adelaide, Australia
        • Recruiting
        • Royal Adelaide Hospital
      • Box Hill, Australia
        • Recruiting
        • Eastern Health - Box Hill Hospital
      • Geelong, Australia
        • Recruiting
        • Barwon Health
      • Perth, Australia
        • Recruiting
        • Royal Perth Hospital
  • Belgium
      • Edegem, Belgium
        • Recruiting
        • Antwerp University Hospital (UZA)
      • Hasselt, Belgium
        • Recruiting
        • Jessa Ziekenhuis
      • Leuven, Belgium
        • Recruiting
        • University Hospital (UZ) Leuven
  • Czechia
      • Nový Hradec Králové, Czechia
        • Recruiting
        • Fakultni nemocnice Hradec Kralove
      • Ostrava, Czechia
        • Recruiting
        • Fakultni Nemocnice Ostrava
      • Prague, Czechia
        • Recruiting
        • Vseobecna fakultni nemocnice v Praze
  • France
      • Nantes, France
        • Recruiting
        • CHU de Nantes - Hôtel-Dieu
      • Rouen, France
        • Recruiting
        • Centre Henri Becquerel
      • Tours, France
        • Recruiting
        • CHRU de Tours - Hôpital Bretonneau
  • Italy
      • Aviano, Italy
        • Recruiting
        • Centro Riferimento Oncologico - Aviano
      • Meldola, Italy
        • Recruiting
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      • Milano, Italy
        • Recruiting
        • Asst Grande Ospedale Metropolitano Niguarda
      • Milano, Italy
        • Recruiting
        • IRCCS Ospedale San Raffaele
      • Pavia, Italy
        • Recruiting
        • Fondazione IRCCS Policlinico San Matteo
      • Verona, Italy
        • Recruiting
        • Centro Ricerche Cliniche Di Verona S.R.L.
  • Korea, Republic of
      • Goyang, Korea, Republic of
        • Recruiting
        • National Cancer Center
      • Incheon, Korea, Republic of
        • Recruiting
        • Gachon University Gil Medical Center
      • Seoul, Korea, Republic of
        • Recruiting
        • Seoul National University Hospital
      • Seoul, Korea, Republic of
        • Recruiting
        • Samsung Medical Center
      • Seoul, Korea, Republic of
        • Recruiting
        • Seoul St. Mary's Hospital
      • Seoul, Korea, Republic of
        • Recruiting
        • Severance Hospital, Yonsei University Health System
  • Poland
      • Gdansk, Poland
        • Recruiting
        • Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
      • Gdańsk, Poland
        • Recruiting
        • Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii
      • Gliwice, Poland
        • Recruiting
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii
      • Krakow, Poland
        • Recruiting
        • Szpital Uniwersytecki Krakow - Oddzial Kliniczny Hematologii
      • Kraków, Poland
        • Recruiting
        • Pratia MCM Krakow
      • Wroclaw, Poland
        • Recruiting
        • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
  • Portugal
      • Braga, Portugal
        • Recruiting
        • Hospital de Braga
      • Lisboa, Portugal
        • Recruiting
        • Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria
      • Lisbon, Portugal
        • Recruiting
        • Champalimaud Cancer Center
      • Porto, Portugal
        • Recruiting
        • Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
      • Vila Nova de Gaia, Portugal
        • Recruiting
        • Centro Hospitalar de Vila Nova de Gaia/Espinho EPE
  • Switzerland
      • Saint Gallen, Switzerland
        • Recruiting
        • Kantonsspital St. Gallen
  • United Kingdom
      • Leeds, United Kingdom
        • Recruiting
        • St James's University Hospital
      • London, United Kingdom
        • Recruiting
        • King's College Hospital
      • London, United Kingdom
        • Recruiting
        • Royal Marsden Foundation Trust
      • Southampton, United Kingdom
        • Recruiting
        • University Hospital Southampton NHS Foundation Trust
  • United States
    • Indiana
      • Goshen, Indiana, United States, 46526
        • Recruiting
        • Goshen Center for Cancer Care
    • Ohio
      • Cincinnati, Ohio, United States, 45221
        • Recruiting
        • University of Cincinnati
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University Comprehensive Cancer Center
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • UT Southwestern Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Cohort 1: Confirmed diagnosis of TP53wt DLBCL (WHO); R/R DLBCL after at least 2 prior lines of treatment or 1 prior for patients who are ineligible for stem cell transplant
  • Cohort 2: Confirmed diagnosis of TP53wt CLL (iwCLL); R/R CLL after at least 1 prior line of treatment
  • ECOG 0 to 2
  • Adequate hematologic, hepatic, and renal functions.

Exclusion Criteria:

  • Prior treatment with any MDM2 inhibitor
  • Prior treatment with any BTK inhibitor

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1 (R/R DLBCL)

KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.

Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth
Drug: acalabrutinib
acalabrutinib is a BTK inhibitor anticancer drug taken by mouth
Other Names:
  • ACP-196
Experimental: Cohort 2 (R/R CLL)

KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.

Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth
Drug: acalabrutinib
acalabrutinib is a BTK inhibitor anticancer drug taken by mouth
Other Names:
  • ACP-196

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Objective Phase 1b:To determine the KRT-232 maximum tolerated dose/ maximum administered dose (MTD/MAD) and recommended Phase 2 Dose (RP2D) in combination with acalabrutinib in subjects with R/R DLBCL or R/R CLL
Time Frame: 56 Days
Endpoint/Outcome Measures: Dose-limiting toxicities will be used to establish the MTD/MAD of KRT-232 in combination with acalabrutinib. The Safety Review Committee will determine the RP2D based on safety data of the combination of KRT-232 and acalabrutinib.
56 Days
Primary Objective Phase 2: Cohort 1: To determine the complete response (CR)
Time Frame: 1 Year
Endpoint/Outcome Measures: Cohort 1: The proportion of subjects with CR as assessed by investigators per the Lugano Classification.
1 Year
Primary Objective Phase 2: Cohort 2: To determine the rate of CR/complete remission with incomplete hematologic recovery (CRi) rate in R/R CLL
Time Frame: 1 Year
Endpoint/Outcome Measures: Cohort 2: The proportion of subjects with CR/CRi as assessed by investigators per iwCLL Response Criteria.
1 Year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
Time Frame: Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2
Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameter from a single dose will be estimated maximum concentration (Cmax).
Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
Time Frame: Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2
Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameters from a single dose will be area under the curve (AUC).
Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
Time Frame: Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2
Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameters from a single dose will be half-life (T1/2).
Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
Time Frame: Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2
Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameter from a single dose will be apparent clearance.
Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
Time Frame: Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2
Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameters from a single dose will be apparent volume of distribution using non-compartmental or compartmental PK methods with the software WinNonlin.
Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2
Phase 2 Secondary Objective: Cohort 1 (R/R DLBCL): To determine the overall response rate (ORR) for R/R DLBCL subjects.
Time Frame: 2 Years
Endpoint/Outcome Measures: The proportion of subjects who achieve a partial response (PR) or better at any time point while on study.
2 Years
Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects
Time Frame: 2 Years
Endpoint/Outcome Measures: The proportion of subjects who achieve a PR or better at any time point while on study, as assessed by iwCLL Response Criteria
2 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kartos Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 23, 2021

Primary Completion (Anticipated)

October 1, 2022

Study Completion (Anticipated)

March 1, 2024

Study Registration Dates

First Submitted

July 27, 2020

First Submitted That Met QC Criteria

August 5, 2020

First Posted (Actual)

August 6, 2020

Study Record Updates

Last Update Posted (Actual)

August 4, 2022

Last Update Submitted That Met QC Criteria

August 3, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KRT-232-111

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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